Active DNA demethylation underlies key facets of reproduction in flowering plants and mammals and serves a general genome housekeeping function in plants. A family of 5-methylcytosine DNA glycosylases catalyzes plant demethylation via the well-known DNA base-excision-repair process. Although the existence of active demethylation has been known for a longer time in mammals, the means of achieving it remain murky and mammals lack counterparts to the plant demethylases. Several intriguing experiments have indicated, but not conclusively proven, that DNA repair is also a plausible mechanism for animal demethylation. Here, we examine what is known from flowering plants about the pathways and function of enzymatic demethylation and discuss possible mechanisms whereby DNA repair might also underlie global demethylation in mammals.